Relationship between the presence of small, dense low-density lipoprotein and plasma lipid phenotypes in Japanese children

To clarify the relationship between the expression of atherogenic small, dense low-density lipoprotein (SDLDL) and underlying lipid metabolic abnormalities, the prevalence of SDLDL in relation to the serum lipid phenotype was analyzed in 229 children. The LDL particle size was measured using gradient gel electrophoresis, and a particle size of less than 25.5 nm was considered to represent SDLDL. The overall prevalence of SDLDL in the sample population was 8.2% (19/229; 11/117 for boys and 8/112 for girls). Hyperlipidemia phenotype IIb (elevated concentrations of both triglyceride [TG] and total cholesterol [TC]) was strongly associated with SDLDL in 83% (5/6) of the subjects. An elevated TG concentration (phenotype IV) was associated with SDLDL in 55% (10/18) of the subjects. The association between hyperlipidemia phenotype IIa (elevated TC but a normal TG concentration) and SDLDL was quite low (2%; 1/56), but SDLDL was detected in 5% (8/155) of the subjects who presented with normolipidemia. Therefore, these findings suggest that the expression of SDLDL is largely related to lipid abnormalities characterized by phenotype IIb or IV, the underlying metabolic abnormality of which is suspected to be insulin resistance; however, an additional mechanism for the formation of SDLDL that functions independently of plasma lipid abnormalities also seems to exist.     

Autoantibodies frequently detected in patients with aplastic anemia

Although accumulating evidence strongly suggests that aplastic anemia (AA) is a T cell-mediated autoimmune disease, no target antigens have yet been described for AA. In autoimmune diseases, target autoantigens frequently induce not only cellular T-cell responses but also humoral B-cell responses. We hypothesized that the presence of antigen-specific autoantibodies could be used as a "surrogate marker" for the identification of target T-cell autoantigens in AA patients. We screened a human fetal liver library for serologic reactivity against hematopoietic stem/progenitor cell antigens and isolated 32 genes. In 7 of 18 AA patients, an immunoglobulin G (IgG) antibody response was detected to one of the genes, kinectin, which is expressed in all hematopoietic cell lineages tested including CD34+ cells. No response to kinectin was detected in healthy volunteers, multiply transfused non-AA patients, or patients with other autoimmune diseases. Epitope mapping of IgG autoantibodies against kinectin revealed that the responses to several of the epitopes were shared by different AA patients. Moreover, CD8+ cytotoxic T cells raised against kinectin-derived peptides suppressed the colony formation of granulocyte macrophage colony-forming units (CFU-GMs) in an HLA class I-restricted fashion. These results suggest that kinectin may be a candidate autoantigen that is involved in the pathophysiology of AA.     

A multi-institutional survey of the effectiveness of chemotherapy combined with radiotherapy for patients with nasopharyngeal carcinoma

BACKGROUND: Previous randomized trials have shown a survival advantage of concurrent platinum-based chemoradiotherapy with or without adjuvant chemotherapy for advanced nasopharyngeal cancer. Applicability of these data to a Japanese population is an important issue which remains to be solved. METHODS: A retrospective survey of treatment of patients with nasopharyngeal cancer in 17 institutions in Japan was done with special reference to the relationship between the type of chemotherapy and survival outcome. Chemotherapy used was classified according to: (i) whether > or =2 courses of platinum plus 5-fluorouracil (FP) was given; or (ii) whether platinum was administered concurrently with radiotherapy (RT). This resulted in three groups being produced consisting of (i)/(ii) = YES/YES, other miscellaneous (MISC) and RT alone. RESULTS: Of 333 evaluable replies, 67 patients (20%) corresponded to the YES/YES, 192 (58%) to the MISC and 74 (22%) to the RT alone group. The YES/YES group achieved a better overall survival than RT alone for patients with intermediate stage (T3N0 or T1-3N1, 81.9 versus 60.7% at 5 years, P = 0.042) and advanced stage (T4 or N2/3, 56.6 versus 31.5%, P = 0.017) disease. The MISC group achieved an almost identical survival rate to that in the YES/YES group for patients with intermediate stage disease (81.9% at 5 years, P = 0.968), whereas it was not significantly different from that of the RT alone group for patients with advanced stage disease (44.0%, P = 0.261). CONCLUSION: The results of this survey mirrored the data from previous randomized trials for patients with intermediate and advanced stage nasopharyngeal cancer in Japan. However, confirmatory prospective trials are required to test the efficacy of less toxic approaches for patients with intermediate stage disease.     

Alteration of zinc concentrations in the brain implanted with C6 glioma

The uptake of zinc, an essential element, is critical not only for cell proliferation but also cell functions. On the basis of the evidence suggesting that preferential uptake of 65Zn in brain tumors may be associated with avid cell proliferation, alteration of zinc concentrations in the brain implanted with C6 glioma was studied by brain autoradiography using 65Zn. After implantation of C6 glioma cells into the hippocampus, 65Zn concentrations in the brain were compared between 1 h and 6 days after intravenous injection of 65ZnCl(2). The 65Zn concentration in the tumor 1 h after the injection was approximately twice as high as that 6 days after the injection. However, the 65Zn concentration in the tumor 6 days after the injection was higher than in any other brain region. These results suggest that zinc taken up in the tumor may be utilized for tumor cell proliferation and that there is greater potential in the use of 69mZn, a short-half life gamma-emitter, for evaluation of the viability of brain tumors.     

Lateralising value of neuropsychological protocols for presurgical assessment of temporal lobe epilepsy

PURPOSE: To estimate the value of neuropsychological measurements in determining the side of seizure onset for presurgical assessment in patients with temporal lobe epilepsy. The lateralising value of neuropsychological protocols was evaluated for all patients and in subpopulations depending on surgical outcome with regard to seizure control, speech dominance, neuropathology, and need for intracranial EEG recordings. METHODS: A battery of neuropsychological procedures was carried out preoperatively in 125 patients who underwent left (n = 66) or right (n = 59) temporal lobectomies. Binary logistic regression analysis was performed to find sets of variables that allowed the best prediction of the side of seizure onset (assumed to be the operated-on side). RESULTS: Combinations of noninvasive neuropsychological tests and Wada subscores showed the highest lateralising values: 80.8% for all patients, 79.4% in seizure-free patients, 86.0% in patients not rendered seizure free, 85.7% in left speech patients, 77.8% in non-left speech patients, 89.3% in patients with mesial temporal sclerosis (MTS), 78.1% in non-MTS patients, 80.3% in patients who underwent intracranial EEG recordings, and 77.3% in those who did not. CONCLUSIONS: The lateralising value (80-90%) of neuropsychological protocols appears similar to that of other tests widely accepted for lateralisation (ictal and interictal scalp EEG and neuroimaging). Attention should be paid to neuropsychological results, particularly from the Wada test, during presurgical assessment of temporal lobe epilepsy, as they can provide strong support for findings from other lateralising tests, particularly in patients with presumed MTS or in left-speech patients.     

Demographic and psychological features of déjà vu experiences in a nonclinical Japanese population

The authors investigated the frequency and correlates of déjà vu experiences in 386 healthy adult volunteers recruited from several areas in Japan. Déjà vu experiences and related experiences were evaluated using the Inventory of Déjà vu Experiences Assessment. Déjà vu experiences were observed by 294 (76.2%) of the 386 participants. Persons who experienced déjà vu were younger and more educated than persons who had not experienced it. There were no differences in the frequency of déjà vu experiences based on sex, hand preference, or area of residence. Subsequent factor analysis associated déjà vu with precognitive dreams and remembering dreams as dream- and memory-related factors rather than with the dissociation-related factors of depersonalization, derealization, jamais vu, and daydreams or with mental activity-related factors such as paranormal quality and travel frequency. Results suggest that déjà vu experiences are associated with good memory function.     

Release of glutamate and GABA in the hippocampus under zinc deficiency

Zinc homeostasis in the brain is affected by dietary zinc deficiency, and its alteration may cause brain dysfunctions. On the basis of the previous evidence that hippocampal zinc was responsive to 12-week zinc deprivation, responsiveness of hippocampal zinc to dietary zinc deficiency was examined in rats fed a zinc-deficient diet for 4 weeks. Zinc concentration in the hippocampus was not decreased by zinc deprivation for 4 weeks. However, Timm's stain was extensively attenuated in the brain of the zinc-deficient rats. In the brain of the zinc-deficient rats, moreover, zinc concentration in the hippocampal extracellular fluid was approximately 30% of that of control rats. These results demonstrate that vesicular zinc is responsive to dietary zinc and may decrease easily under zinc deficiency. Zinc concentration in the hippocampal extracellular fluid during stimulation with high K(+) was significantly increased even in zinc-deficient rats, although the increased levels of zinc were lower than the basal levels of zinc in control rats. The basal glutamate concentration in the hippocampal extracellular fluid was not significantly different between the control and zinc-deficient rats. However, glutamate concentration in the hippocampal extracellular fluid during stimulation with high K(+) was more increased in the zinc-deficient rats than in the control rats. Gamma aminobutyric acid (GABA) concentration in the hippocampal extracellular fluid during stimulation with high K(+) was increased in the control rats, but not in the zinc-deficient rats. The present study suggests that the excitability of hippocampal glutamatergic neurons is enhanced by dietary zinc deficiency.     

Selection of surrogate marker genes in primary central nervous system lymphomas for radio-chemotherapy by DNA array analysis of gene expression profiles

Primary central nervous system lymphomas (PCNSLs) are extra nodal B-cell non-Hodgkin's lymphomas with primary manifestation in the brain, and their incidence has been increasing among both immunocompetent and immunocompromised populations. Samples of oligodendroglioma (n=5), glioblastoma (n=7), PCNSL (n=6), and normal brain (n=3) were studied (total of 21 samples) using cDNA array technology. The hierarchical clustering algorithm was used to obtain a phylogenetic tree, and it revealed a striking feature: PCNSL was clearly separated. The genes encoding laminin receptor 2, thioredoxin peroxidase, and elongation factor-1 were selected as specific genes in PCNSL by principal component analysis (PCA). When Mann-Whitney tests were performed to identify genes responsible for the differences between responders and non-responders to the treatment schedule for PCNSL, 76 known genes were found to show significantly different expression patterns between the two groups at the P<0.01 level. The two groups were clearly separated by the re-clustering method using the selected genes related to response to chemo-radiotherapy. This is the first report describing the gene expression profiles of PCNSL. In conclusion, accumulation of data with respect to the expression profiles of PCNSL specimens, clinicopathological data, susceptibility to treatment, and outcome will provide information for identifying optimal therapeutic modalities for individual patients and novel therapeutic targets.     

Usefulness of urinary NMP22 to detect tumor recurrence of superficial bladder cancer after transurethral resection

Background In a prospective study we compared the usefulness of urinary nuclear matrix protein 22 (NMP22) with that of urine cytology and other urinary markers in the monitoring of superficial bladder cancer after transurethral resection (TURBT).Methods The subjects were 156 patients, comprising 99 patients with superficial bladder cancer in whom TURBT was planned (untreated group) and 57 patients without tumors in the bladder who had been followed up after TURBT (follow-up group).Results Among the 156 patients, who were monitored for 11–26 months (median, 21 months), recurrence was observed in 51 patients (33.0%). At the time of recurrence, the sensitivities of NMP22, basic fetoprotein (BFP), and bladder tumor antigen (BTA) tests, and urine cytology were 18.6%, 23.3%, 9.3%, and 7.0%, respectively. The factors affecting the sensitivity of NMP22 were tumor size and urinary WBC. The size of recurrent tumors was significantly smaller (P 0.05) than that of the initial tumors. Based on receiver operating characteristic (ROC) curves calculated from the data of patients with recurrence, the ideal cutoff values at recurrence were recommended to be 5.0U/ml for NMP22 and 6.0ng/ml for BFP. Using these cutoff values, the sensitivities of NMP22 and BFP were 48.8% and 44.2%, respectively.Conclusions Because the size of recurrent bladder tumors is usually smaller than that of the initial tumors, the cutoff values of urinary markers should be reduced to detect these tumors. We recommend 5.0U/ml as a cutoff value of NMP22 for detection of recurrence of bladder tumor.     

Validity of a five-minute speech sample for the measurement of expressed emotion in the families of Japanese patients with mood disorders

Both the Camberwell Family Interview (CFI) and the Five-Minute Speech Sample (FMSS) have been used to define expressed emotion (EE), but the validity of the FMSS relative to the CFI in mood disorders has not been evaluated. In our study, the FMSS and the CFI were performed on the same day in close family members of inpatients with mood disorders within 2 weeks after their admission. The ratings obtained from the CFI were then used to estimate the validity of the FMSS, which was defined by sensitivity and specificity on the basis of the overall evaluation of EE. Validity was also assessed by including borderline ratings of 'low EE' in the category of 'high EE.' Based on the overall evaluation, sensitivity and specificity were 66.7 and 96.8%, respectively. When borderline low EE was included in high EE, the sensitivity and specificity were 100 and 90.3%, respectively. The validity of definitions of EE by the FMSS relative to the CFI was high in mood disorders. Evaluation of EE by the FMSS, which is clinically applicable to patients with mood disorders, is feasible. The validity of this approach is enhanced when families defined as 'borderline low EE' are included in the high-EE category.